Role of Go/i subgroup of G proteins in olfactory signaling of Drosophila melanogaster.

Intracellular signaling in insect olfactory receptor neurons remains unclear, with both metabotropic and ionotropic components being discussed. Here, we investigated the role of heterotrimeric Go and Gi proteins using a combined behavioral, in vivo and in vitro approach. Specifically, we show that inhibiting Go in sensory neurons by pertussis toxin leads to behavioral deficits. We heterologously expressed the olfactory receptor dOr22a in human embryonic kidney cells (HEK293T). Stimulation with an odor led to calcium influx, which was amplified via calcium release from intracellular stores. Subsequent experiments indicated that the signaling was mediated by the Gβγ subunits of the heterotrimeric Go/i proteins. Finally, using in vivo calcium imaging, we show that Go and Gi contribute to odor responses both for the fast (phasic) as for the slow (tonic) response component. We propose a transduction cascade model involving several parallel processes, in which the metabotropic component is activated by Go and Gi , and uses Gβγ.

El estado del stock de anchoveta y recomendaciones para el año pesquero 1968/69

Brinda información sobre las capturas del recurso anchoveta del año 1967/68, la cual indica que llegó a una cifra récord alcanzando 9'817,768 toneladas métricas del recurso. A su vez, menciona las ocurrencias que afectaron la comercialización del recurso, tales como: Paralización de fábricas, días de paro y día de vea del recurso por la temporada de verano.

Drogues récréatives: le plaisir des complications [Recreational drugs: the complication's pleasure?].

Steadily increasing since 1990, the use of psychoactive substances was expanded to new designer drugs (bath salts, spice) with so original still unknown pharmacological effects. At the beginning, the pleasure, first feeling, turns sometimes, in acute medical emergency and then, in some cases, in chronic diseases. Side expected or not desired effects, seen in emergency departments could be necrotizing gangrene among consumers Krokodil or dystonic reactions in consumers of Spice. Moreover, adulterants could increase the dangerosity of the substances. Searching a toxidrome helps to find the incrimining substance.

Test of four colon cancer risk-scores in formalin fixed paraffin embedded microarray gene expression data.

BACKGROUND: Prognosis prediction for resected primary colon cancer is based on the T-stage Node Metastasis (TNM) staging system. We investigated if four well-documented gene expression risk scores can improve patient stratification. METHODS: Microarray-based versions of risk-scores were applied to a large independent cohort of 688 stage II/III tumors from the PETACC-3 trial. Prognostic value for relapse-free survival (RFS), survival after relapse (SAR), and overall survival (OS) was assessed by regression analysis. To assess improvement over a reference, prognostic model was assessed with the area under curve (AUC) of receiver operating characteristic (ROC) curves. All statistical tests were two-sided, except the AUC increase. RESULTS: All four risk scores (RSs) showed a statistically significant association (single-test, P < .0167) with OS or RFS in univariate models, but with HRs below 1.38 per interquartile range. Three scores were predictors of shorter RFS, one of shorter SAR. Each RS could only marginally improve an RFS or OS model with the known factors T-stage, N-stage, and microsatellite instability (MSI) status (AUC gains < 0.025 units). The pairwise interscore discordance was never high (maximal Spearman correlation = 0.563) A combined score showed a trend to higher prognostic value and higher AUC increase for OS (HR = 1.74, 95% confidence interval [CI] = 1.44 to 2.10, P < .001, AUC from 0.6918 to 0.7321) and RFS (HR = 1.56, 95% CI = 1.33 to 1.84, P < .001, AUC from 0.6723 to 0.6945) than any single score. CONCLUSIONS: The four tested gene expression-based risk scores provide prognostic information but contribute only marginally to improving models based on established risk factors. A combination of the risk scores might provide more robust information. Predictors of RFS and SAR might need to be different.

The dark sides of capillary morphogenesis gene 2.

Capillary morphogenesis gene 2 (CMG2) is a type I membrane protein involved in the homeostasis of the extracellular matrix. While it shares interesting similarities with integrins, its exact molecular role is unknown. The interest and knowledge about CMG2 largely stems from the fact that it is involved in two diseases, one infectious and one genetic. CMG2 is the main receptor of the anthrax toxin, and knocking out this gene in mice renders them insensitive to infection with Bacillus anthracis spores. On the other hand, mutations in CMG2 lead to a rare but severe autosomal recessive disorder in humans called Hyaline Fibromatosis Syndrome (HFS). We will here review what is known about the structure of CMG2 and its ability to mediate anthrax toxin entry into cell. We will then describe the limited knowledge available concerning the physiological role of CMG2. Finally, we will describe HFS and the consequences of HFS-associated mutations in CMG2 at the molecular and cellular level.

Perceptual and semantic contributions to repetition priming of environmental sounds.

Repetition of environmental sounds, like their visual counterparts, can facilitate behavior and modulate neural responses, exemplifying plasticity in how auditory objects are represented or accessed. It remains controversial whether such repetition priming/suppression involves solely plasticity based on acoustic features and/or also access to semantic features. To evaluate contributions of physical and semantic features in eliciting repetition-induced plasticity, the present functional magnetic resonance imaging (fMRI) study repeated either identical or different exemplars of the initially presented object; reasoning that identical exemplars share both physical and semantic features, whereas different exemplars share only semantic features. Participants performed a living/man-made categorization task while being scanned at 3T. Repeated stimuli of both types significantly facilitated reaction times versus initial presentations, demonstrating perceptual and semantic repetition priming. There was also repetition suppression of fMRI activity within overlapping temporal, premotor, and prefrontal regions of the auditory "what" pathway. Importantly, the magnitude of suppression effects was equivalent for both physically identical and semantically related exemplars. That the degree of repetition suppression was irrespective of whether or not both perceptual and semantic information was repeated is suggestive of a degree of acoustically independent semantic analysis in how object representations are maintained and retrieved.

Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy.

BACKGROUND: Both induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer. METHODS: Patients with resectable advanced squamous cell carcinoma of the larynx (tumor stage T3-T4) or hypopharynx (T2-T4), with regional lymph nodes in the neck staged as N0-N2 and with no metastasis, were randomly assigned to treatment in the sequential (or control) or the alternating (or experimental) arm. In the sequential arm, patients with a 50% or more reduction in primary tumor size after two cycles of cisplatin and 5-fluorouracil received another two cycles, followed by radiotherapy (70 Gy total). In the alternating arm, a total of four cycles of cisplatin and 5-fluorouracil (in weeks 1, 4, 7, and 10) were alternated with radiotherapy with 20 Gy during the three 2-week intervals between chemotherapy cycles (60 Gy total). All nonresponders underwent salvage surgery and postoperative radiotherapy. The Kaplan-Meier method was used to obtain time-to-event data. RESULTS: The 450 patients were randomly assigned to treatment (224 to the sequential arm and 226 to the alternating arm). Median follow-up was 6.5 years. Survival with a functional larynx was similar in sequential and alternating arms (hazard ratio of death and/or event = 0.85, 95% confidence interval = 0.68 to 1.06), as were median overall survival (4.4 and 5.1 years, respectively) and median progression-free interval (3.0 and 3.1 years, respectively). Grade 3 or 4 mucositis occurred in 64 (32%) of the 200 patients in the sequential arm who received radiotherapy and in 47 (21%) of the 220 patients in the alternating arm. Late severe edema and/or fibrosis was observed in 32 (16%) patients in the sequential arm and in 25 (11%) in the alternating arm. CONCLUSIONS: Larynx preservation, progression-free interval, and overall survival were similar in both arms, as were acute and late toxic effects.

FAM161A, associated with retinitis pigmentosa, is a component of the cilia-basal body complex and interacts with proteins involved in ciliopathies.

Retinitis pigmentosa (RP) is a retinal degenerative disease characterized by the progressive loss of photoreceptors. We have previously demonstrated that RP can be caused by recessive mutations in the human FAM161A gene, encoding a protein with unknown function that contains a conserved region shared only with a distant paralog, FAM161B. In this study, we show that FAM161A localizes at the base of the photoreceptor connecting cilium in human, mouse and rat. Furthermore, it is also present at the ciliary basal body in ciliated mammalian cells, both in native conditions and upon the expression of recombinant tagged proteins. Yeast two-hybrid analysis of binary interactions between FAM161A and an array of ciliary and ciliopathy-associated proteins reveals direct interaction with lebercilin, CEP290, OFD1 and SDCCAG8, all involved in hereditary retinal degeneration. These interactions are mediated by the C-terminal moiety of FAM161A, as demonstrated by pull-down experiments in cultured cell lines and in bovine retinal extracts. As other ciliary proteins, FAM161A can also interact with the microtubules and organize itself into microtubule-dependent intracellular networks. Moreover, small interfering RNA-mediated depletion of FAM161A transcripts in cultured cells causes the reduction in assembled primary cilia. Taken together, these data indicate that FAM161A-associated RP can be considered as a novel retinal ciliopathy and that its molecular pathogenesis may be related to other ciliopathies.

Mfn2 downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death.

Mitochondrial fusion and fission is a dynamic process critical for the maintenance of mitochondrial function and cell viability. During excitotoxicity neuronal mitochondria are fragmented, but the mechanism underlying this process is poorly understood. Here, we show that Mfn2 is the only member of the mitochondrial fusion/fission machinery whose expression is reduced in in vitro and in vivo models of excitotoxicity. Whereas in cortical primary cultures, Drp1 recruitment to mitochondria plays a primordial role in mitochondrial fragmentation in an early phase that can be reversed once the insult has ceased, Mfn2 downregulation intervenes in a delayed mitochondrial fragmentation phase that progresses even when the insult has ceased. Downregulation of Mfn2 causes mitochondrial dysfunction, altered calcium homeostasis, and enhanced Bax translocation to mitochondria, resulting in delayed neuronal death. We found that transcription factor MEF2 regulates basal Mfn2 expression in neurons and that excitotoxicity-dependent degradation of MEF2 causes Mfn2 downregulation. Thus, Mfn2 reduction is a late event in excitotoxicity and its targeting may help to reduce excitotoxic damage and increase the currently short therapeutic window in stroke.

Genetic manipulation of adult-born hippocampal neurons rescues memory in a mouse model of Alzheimer's disease.

In adult mammals, neural progenitors located in the dentate gyrus retain their ability to generate neurons and glia throughout lifetime. In rodents, increased production of new granule neurons is associated with improved memory capacities, while decreased hippocampal neurogenesis results in impaired memory performance in several memory tasks. In mouse models of Alzheimer's disease, neurogenesis is impaired and the granule neurons that are generated fail to integrate existing networks. Thus, enhancing neurogenesis should improve functional plasticity in the hippocampus and restore cognitive deficits in these mice. Here, we performed a screen of transcription factors that could potentially enhance adult hippocampal neurogenesis. We identified Neurod1 as a robust neuronal determinant with the capability to direct hippocampal progenitors towards an exclusive granule neuron fate. Importantly, Neurod1 also accelerated neuronal maturation and functional integration of new neurons during the period of their maturation when they contribute to memory processes. When tested in an APPxPS1 mouse model of Alzheimer's disease, directed expression of Neurod1 in cycling hippocampal progenitors conspicuously reduced dendritic spine density deficits on new hippocampal neurons, to the same level as that observed in healthy age-matched control animals. Remarkably, this population of highly connected new neurons was sufficient to restore spatial memory in these diseased mice. Collectively our findings demonstrate that endogenous neural stem cells of the diseased brain can be manipulated to become new neurons that could allow cognitive improvement.

PTH and 1.25 vitamin D response to a low-calcium diet is associated with bone mineral density in renal stone formers.

BACKGROUND: Renal calcium stones and hypercalciuria are associated with a reduced bone mineral density (BMD). Therefore, the effect of changes in calcium homeostasis is of interest for both stones and bones. We hypothesized that the response of calciuria, parathyroid hormone (PTH) and 1.25 vitamin D to changes in dietary calcium might be related to BMD. METHODS: A single-centre prospective interventional study of 94 hyper- and non-hypercalciuric calcium stone formers consecutively retrieved from our stone clinic. The patients were investigated on a free-choice diet, a low-calcium diet, while fasting and after an oral calcium load. Patient groups were defined according to lumbar BMD (z-score) obtained by dual X-ray absorptiometry (group 1: z-score <-0.5, n = 30; group 2: z-score -0.5-0.5, n = 36; group 3: z-score >0.5, n = 28). The effect of the dietary interventions on calciuria, 1.25 vitamin D and PTH in relation to BMD was measured. RESULTS: An inverse relationship between BMD and calciuria was observed on all four calcium intakes (P = 0.009). On a free-choice diet, 1.25 vitamin D and PTH levels were identical in the three patient groups. However, the relative responses of 1.25 vitamin D and PTH to the low-calcium diet were opposite in the three groups with the highest increase of 1.25 vitamin D in group 1 and the lowest in group 3, whereas PTH increase was most pronounced in group 3 and least in group 1. CONCLUSION: Calcium stone formers with a low lumbar BMD exhibit a blunted response of PTH release and an apparently overshooting production of 1.25 vitamin D following a low-calcium diet.

Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function.

In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10(-9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10(-4)-2.2 × 10(-7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.

Bulles de papes. Titres des maisons de LA JUGIE (1313-1623). — MELANGES (1222-1623).

Contient : Titres de la Jugie ; N° 623 (1) Contrat de mariage de Jacques de la Jugie et de Guillemette de la Borgayrie (23 juillet 1313) ; copie du 18 mars 1314 a. st ; N° 624 (2) Contrat de mariage de Pierre de la Jugie et de Jeanne Pebeyre (août1316) ; restes de sceau sur simple queue ; N° 625 (3) Testament de Geraud de Rajaut, de Tulle, damoiseau (9 août 1329) ; N° 626 (4) Contrat de mariage de Gui Aimoin de Puydeval et d'Hélie de la Jugie (14 décembre 1339) ; N° 627 (5) Donation de biens faite par Guillemette de la Limosnie à Gui de Puydeval, son oncle (30 janvier 1351) ; copie du XVIIe siècle ; N° 628 (6) Accord entre Archambaud, vicomte de Comborn, et Gui de Puydeval (24 mai 1351) ; copie contemporaine ; N° 629 (7) Contrat de mariage de Raimond de Bossac et de Marie de Puydeval (2 août 1352) ; N° 630 (8) Testament de Gui de Puydeval (26 janvier 1371 a. st.) ; copie du XVIIe siècle ; N° 631 (9) Testament de Nicolas de la Jugie, seigneur de Levinerie (26 mars 1374 a. st.) ; vidimus du 18 mai 1402 ; N° 632 (10) Testament de Guillaume de la Jugie, alias de Puydeval (20 août 1397) ; N° 633 (11) Testament d'Aelis de la Jugie (19 juillet 1409) ; N° 634 (12) Décisions prises par divers seigneurs du Limousin, relativement à l'expédition contre les Anglais, pour la levée du siège d'Auberoche (4 septembre 1419) ; N° 635 (13) Contrat de mariage d'Aimar de Puydeval et de Marguerite de Gimel (12 juillet 1426) ; N° 636 (14) Testament d'Hélène de Puydeval, veuve de Jean « de Sadone » (2 juin 1436) ; N° 637 (15) Testament de Jean de la Jugie, alias de Puydeval (7 décembre 1461) ; N° 638 (16) Contrat de mariage de Jean de Sourries, seigneur de Vaur, et d'Anne de Puydeval (29 janvier 1492 a. st.) ; copie, papier ; N° 639 (17) Testament d'Antoine de Puydeval (9 octobre 1495) ; copie du 28 mars 1502, a. st ; N° 640 (18) Contrat de mariage de Pons de Gourdon, seigneur de La Roque, et de Françoise de Puydeval (20 janvier 1497 a. st.) ; copie du 23 août 1579 ; N° 641 (19) Quittance générale donnée par Blanche de Malesec, veuve d'Antoine de Puydeval, à Gilles de Malesec, son frère (23 juin 1512) ; N° 642 (20) Testament de Gabrielle de Puydeval, dame de Miremont (20 mars 1516-1517) ; copie du XVIe siècle ; N° 643 (21) Testament de Denis de Puydeval (18 août 1523) ; copie du XVIe siècle ; N° 644 (22) Quittance générale donnée à Géraud de Puydeval par Pierre de Rajaut et Anne de Puydeval sa femme, 2 août 1534 ; N° 645 (23) Contrat de mariage de Rigaut de Saint-Martial, baron de Conros, et de Françoise de Puydeval (18 juin 1559) ; copie du 22 juillet 1583 ; N° 646 (24) Testament de Géraud de Puydeval (20 mai 1563) ; N° 647 (25) Procès-verbal de visite de bois faite par les arbitres choisis par les seigneurs de Puydeval et de Vaur (5 janvier 1564) ; N° 648 (26) Accord entre Géraud de Puydeval et Bonaventure de Sourries, seigneur de Vaur, au sujet du lieu de La Reynie (21 novembre 1560) ; N° 649 (27) Accord entre Anne de Puydeval, veuve de Jean de Sourries, seigneur de Vaur, et Bonaventure de Sourries (27 septembre 1559) ; N° 650 (28) Testament d'Anne de Puydeval, veuve de Jean [de Sourries, seigneur de] Vaur (8 septembre 1555) ; N° 651 (29) Testament de Jean de Puydeval, doyen de l'église de Tulle ; N° 652 (30) Testament de Françoise de Puydeval, veuve de Rigaut de Saint-Marsal, baron de Conros (16 juin 1601) ; N° 653 (31) Autre testament de ladite dame (22 août 1604) ; N° 654 Copie du précédent testament ; N° 655 (32) Accord entre Josias de Cosnac, seigneur d'Assy, et sa soeur, Marie de Cosnac, femme de Henry de Puydeval, baron de Conros (31 mars 1623 ; N° 656 (33) Contrat de mariage de Pierre de Soudeilles et d'Anne de Puydeval (s. d.) ; N° 657 (33 bis) Copie de la pièce précédente ; Mélanges ; N° 658 (1) Accord entre Guillaume, évêque de Paris, et son chapitre, d'une part, et Philippe-Auguste, de l'autre, au sujet des droits de l'église de Paris (décembre 1222) ; N° 659 (2) Accord entre Philippe le Bel et l'église de Paris pour l'affectation de certaines redevances à la réparation des ponts de la Seine (mars 1296-1297) ; N° 660 (3) Décret de l'Université de Paris établissant des règlements pour le collège de Narbonne, à Paris (4 octobre 1377) ; N° 661 (4) Sentence rendue par Jean, abbé de Saint-Taurin d'Evreux, sur le procès entre Jacques Sacquespée, docteur en médecine, et Jean Daigny, chanoine de la Sainte-Chapelle de Paris (15 mai 1428) ; N° 662 (15) Articles de la Ligue (s. d. [1586 (?)]) ; N° 663 (6) Privilèges accordés par Louis, comte de Flandre, aux marchands castillans trafiquant en Flandre (15 avril 1366) ; copie du XVe siècle ; N° 664 (7) Serment prêté au duc d'Alençon par le chapitre de Cambrai (20 août 1580) ; N° 665 (8) Serment prêté au même personnage par les échevins de la ville de Cambrai (même date) ; N° 666 (9) Aveu rendu à Henri, comte de Rodez, par Pierre de Panat, pour divers fiefs, (juillet 1280) ; N° 667 (10) Aveu rendu par Bernard, comte d'Armagnac et de Rodez, à Guillaume, évêque de Mende, pour les fiefs tenus par ledit comte dans ce diocèse (2 mai 1309) ; N° 668 (11) Autorisation donnée par l'archevêque Michel et le chapitre d'Arles à Jean [de Matha], fondateur de l'Ordre de la Trinité, d'établir une église et un cimetière dans la ville d'Arles (novembre 1203) ; N° 669 (12) Charte de G[uillaume], comte de Forcalquier, abandonnant divers droits à l'église de Ganagobie (10 juin 1206) ; à la suite est transcrite une lettre de A., prieur du dit lieu, à G[uillaume], abbé de Cluny, relative à la donation précédente ; N° 670 (13) Lettres de Charles II, roi de Sicile, comte de Provence, chargeant Hugues de Voisines, senéchal de Provence, de faire sortir du royaume de France la somme de 50.000 livres autorisée par le Roi (24 mars 1297) ; N° 671 (14) Lettres de l'empereur Henri VII, autorisant Gaillard, archevêque d'Arles, à poursuivre la révocation des aliénations de biens ecclésiastiques consenties par ses prédécesseurs (9 juillet 1312) ; N° 672 (15) Lettres de Jean de Clermont, cardinal-évêque de Tusculum, légat du pape dans les provinces de Vienne, Aix, etc., chargeant Jean Ferrier, archevêque d'Arles, de l'assister dans ses fonctions (9 juillet 1533) ; N° 673 (16) Lettres de Raoul de Sendelay, trésorier d'Angleterre, portant donation de terres près de Rouen à Michel de Paris, son ancien serviteur (3 janvier 1445-1446) ; N° 674 (17) Lettre de l'empereur Ferdinand au pape Urbain VIII (28 avril 1635) ; N° 675 (18) Aveu rendu à Bernard, abbé de Charroux, par Jean de Rochefort, pour le château de Saint-Angel (18 mai 1393) ; copie du 17 juillet 1407 ; N° 676 (19) Lettres de l'Université d'Avignon conférant à Pierre Charpin le titre de docteur en droit canon (16 septembre 1405) ; N° 677 (20) Contrat de mariage de Charles d'Apchon, vicomte de Mirmont, et de Lucrèce de Gadaigne (3 août 1579) ; N° 678 (21) Procuration donnée par Philippe de Commynes à Baude Talboein, son secrétaire (9 mars 1474) ; signature autographe ; N° 679 (22) Ratification par Galéas-Marie Sforza du traité conclu en son nom à Amboise entre Tristan Sforza et Louis XI (21 avril 1468) ; N° 680 (23) Lettres d'Etat accordées par le roi Charles VI à Lermite, seigneur de La Faye, son chambellan, envoyé en Angleterre (28 octobre 1407) ; copie du 4 novembre 1407 ; papier ; N° 681 (24) « Plaintes sur le trépas du sage et vertueux chevalier... Jean de La Roche-Aymon ; » pièce de vers (s. d. [1522]) ; miniature en tête ; N° 682 (25) Lettres de Raimond « de Poioliis », archidiacre de Périgueux, recteur du duché de Spolète, pour le paiement de la compagnie de Guillaume de Primat ; N° 683 (26) Lettres de l'Université d'Orléans accordant à Hugues Berthelot le titre de bachelier en droit canon (28 juillet 1409) ; N° 684 (27) Lettres de l'Université d'Orléans au prieur de Marcigny, pour faire pourvoir d'un bénéfice Raoul « Druci », prêtre, licencié en décret (2 septembre 1460 ; N° 685 (28) Lettres de l'Université de Paris à l'abbé de Cluny, pour faire pourvoir d'un bénéfice Jean de Mont, maître ès arts et bachelier en théologie (3 mars 1478-1479) ; N° 686 (29) Lettres de l'Université de Paris à l'abbé de Cluny pour faire pourvoir d'un bénéfice Jean Paulain, maître ès arts (21 février 1538-1539) ; N° 687 (30) Testament de Jacques de Plaigne, seigneur dudit lieu (5 mars 1551-1552) ; copie contemporaine ; N° 688 (31) Contrat de mariage de Pierre de Guasquet et de Marguerite d'Henry (31 mars 1581) ; copie contemporaine ; N° 689 (32) Testament d'Antoine de Guasquet, seigneur de Paramelle (30 août 1585) ; copie contemporaine ; N° 690 (33) Testament de Jean Chantois, sieur de Laumosnerie (30 septembre 1617) ; copie contemporaine ; N° 691 (34) Testament de Claude des Rozières, seigneur de Cherouac (octobre 1623) ; copie contemporaine ; N° 692 (35) Délibération de l'assemblée du clergé de la ville de Reims au sujet de la répartition des deniers à lever sur ledit clergé (30 mars 1585) ; N° 693 (36) Lettre de J[ean de] C[andida] à [Denis Briçonnet], évêque de Saint-Malo (16 novembre, s. d.)

The functional neuroimaging correlates of psychogenic versus organic dystonia.

The neurobiological basis of psychogenic movement disorders remains poorly understood and the management of these conditions difficult. Functional neuroimaging studies have provided some insight into the pathophysiology of disorders implicating particularly the prefrontal cortex, but there are no studies on psychogenic dystonia, and comparisons with findings in organic counterparts are rare. To understand the pathophysiology of these disorders better, we compared the similarities and differences in functional neuroimaging of patients with psychogenic dystonia and genetically determined dystonia, and tested hypotheses on the role of the prefrontal cortex in functional neurological disorders. Patients with psychogenic (n = 6) or organic (n = 5, DYT1 gene mutation positive) dystonia of the right leg, and matched healthy control subjects (n = 6) underwent positron emission tomography of regional cerebral blood flow. Participants were studied during rest, during fixed posturing of the right leg and during paced ankle movements. Continuous surface electromyography and footplate manometry monitored task performance. Averaging regional cerebral blood flow across all tasks, the organic dystonia group showed abnormal increases in the primary motor cortex and thalamus compared with controls, with decreases in the cerebellum. In contrast, the psychogenic dystonia group showed the opposite pattern, with abnormally increased blood flow in the cerebellum and basal ganglia, with decreases in the primary motor cortex. Comparing organic dystonia with psychogenic dystonia revealed significantly greater regional blood flow in the primary motor cortex, whereas psychogenic dystonia was associated with significantly greater blood flow in the cerebellum and basal ganglia (all P < 0.05, family-wise whole-brain corrected). Group × task interactions were also examined. During movement, compared with rest, there was abnormal activation in the right dorsolateral prefrontal cortex that was common to both organic and psychogenic dystonia groups (compared with control subjects, P < 0.05, family-wise small-volume correction). These data show a cortical-subcortical differentiation between organic and psychogenic dystonia in terms of regional blood flow, both at rest and during active motor tasks. The pathological prefrontal cortical activation was confirmed in, but was not specific to, psychogenic dystonia. This suggests that psychogenic and organic dystonia have different cortical and subcortical pathophysiology, while a derangement in mechanisms of motor attention may be a feature of both conditions.

Variability in urinary oxalate measurements between six international laboratories.

BACKGROUND: Hyperoxaluria is a major risk factor for kidney stone formation. Although urinary oxalate measurement is part of all basic stone risk assessment, there is no standardized method for this measurement. METHODS: Urine samples from 24-h urine collection covering a broad range of oxalate concentrations were aliquoted and sent, in duplicates, to six blinded international laboratories for oxalate, sodium and creatinine measurement. In a second set of experiments, ten pairs of native urine and urine spiked with 10 mg/L of oxalate were sent for oxalate measurement. Three laboratories used a commercially available oxalate oxidase kit, two laboratories used a high-performance liquid chromatography (HPLC)-based method and one laboratory used both methods. RESULTS: Intra-laboratory reliability for oxalate measurement expressed as intraclass correlation coefficient (ICC) varied between 0.808 [95% confidence interval (CI): 0.427-0.948] and 0.998 (95% CI: 0.994-1.000), with lower values for HPLC-based methods. Acidification of urine samples prior to analysis led to significantly higher oxalate concentrations. ICC for inter-laboratory reliability varied between 0.745 (95% CI: 0.468-0.890) and 0.986 (95% CI: 0.967-0.995). Recovery of the 10 mg/L oxalate-spiked samples varied between 8.7 ± 2.3 and 10.7 ± 0.5 mg/L. Overall, HPLC-based methods showed more variability compared to the oxalate oxidase kit-based methods. CONCLUSIONS: Significant variability was noted in the quantification of urinary oxalate concentration by different laboratories, which may partially explain the differences of hyperoxaluria prevalence reported in the literature. Our data stress the need for a standardization of the method of oxalate measurement.